Abstract: A latching microregulator for regulating liquid flow on micro-scale levels comprises a substrate having an inlet port and an outlet port, a valve element defining a valve chamber for opening and closing the inlet port, and an actuator assembly for actuating the valve element. The valve chamber is configured to contain a volume of fluid, and the inlet port and the outlet port are in fluid communication with the valve chamber to provide a liquid flow path through the chamber. The actuator assembly comprises a cantilever beam for moving the valve element between an open position and a closed position, an actuator, such as a piezoelectric element, for moving the cantilever beam, and a latch, such as a permanent magnet, for securing the cantilever beam in the closed position. A flow regulation system comprises a plurality of fluid channels of varied flow conductance and a plurality of latching microregulators for selectively blocking or allowing flow through each of the fluid channels.

Abstract: In accordance with the present invention is provided a device and method for delivering DNA for the purpose of gene therapy to specific regions within and around the eye.

Abstract: A method for in vivo electrotherapy, or electroporation-mediated therapy, using a needle array apparatus is provided. Treatment of tumors with a combination of electroporation using the apparatus of the invention, and a chemotherapeutic agent, caused regression of tumors in vivo.

Abstract: The manipulator includes a support and at least one member affixed to and extending away from the support. The member has at least two differentially activatable areas of conductivity. The members are configured to establish a first electromagnetic field in vivo between selected areas of conductivity sufficient to manipulate a molecule relative to a target tissue and to establish a second, typically higher, electromagnetic field sufficient to cause transient permeability of a cell membrane within the target tissue. Restraining means are also described for restricting movement of the members with relation to each other. One method of using the device is for enhancing the delivery of a molecule into a tissue site; another is for poration of the tissue alone or in combination with the migration. The target tissue may include a tumor, organ, or wound site.

Abstract: The present invention provides a method and apparatus adapted to facilitate the entry of a preselected molecule into the intracellular space of a cellular sample through the use of ions generated by a corona charge source. With the present method and apparatus, molecules are manipulated within cells and in the extracellular space surrounding the cells. Manipulation enhances the permeability of cell barriers to allow the subsequent introduction of molecules of interest into the interior of a cell.

Abstract: A PDGF receptor tyrosine kinase inhibitor, especially a 4-(4-methylpiperazin-1-ylmethyl)-N-[4-methyl-3-(4-pyridin-3-yl)pyrimidin-2-ylamino)phenyl]-benzamide of the formula I or a pharmaceutically acceptable salt thereof can be used in the treatment of angiotensin II-induced diseases and a combination which comprises (a) a PDGF receptor tyrosine kinase inhibitor preferably N-{5-[4-(4-methyl-piperazino-methyl)-benzoylamido]-2-methylphenyl}-4-(3-pyridyl)-2-pyrimidine-amine and (b) at least one compound selected from an antihypertensive, an aldosterone antagonist, an aldosterone synthase inhibitor and/or an angiotensin receptor blocker agent and optionally at least one pharmaceutically acceptable carrier for simultaneous, separate or sequential use, in particular for the treatment of hypertension and hypertension-induced diseases.

Abstract: The invention relates to a reconstituted smoking material which comprises a non-polyol aerosol generator, tobacco (optional), binder (optional) and inorganic filler. A further polyol aerosol generator may also be contained in the smoking material. There is also provided a smoking article containing such material in a conventional arrangement or with a core axially disposed within an annulus. A further aspect of the invention is the provision of a polyol or non-polyol aerosol generator disposed in the filter element of a smoking article, which may contain the inventive smoking material. The aerosol material on the filter is eluted into the aerosol of the smoke on burning of the smoking article.

Abstract: A system and method for integrating microfluidic components in a microfluidic system enables the microfluidic system to perform a selected microfluidic function. A capping module includes a microfluidic element for performing a microfluidic function. The capping module is stacked on a microfluidic substrate having microfluidic plumbing to incorporate the microfluidic function into the system.

Abstract: A microfluidic system includes a bubble valve for regulating fluid flow through a microchannel. The bubble valve includes a fluid meniscus interfacing the microchannel interior and an actuator for deflecting the membrane into the microchannel interior to regulate fluid flow. The actuator generates a gas bubble in a liquid in the microchannel when a sufficient pressure is generated on the membrane.

Abstract: The present invention is a device for electromanipulation of chemical species in vivo relative to a target tissue including a nonconductive, conformable array base adapted to be placed coincident to the target tissue, a plurality of electrode elements projecting from the array base towards the target tissue, the electrode elements addressable individually, an electrical source coupled to the plurality of electrodes, a control means interposed between the electrical source and the plurality of electrode elements and in circuit communication therein, the control means adapted to establish an electrical potential between at least two electrodes, and a delivery means adapted to introduce chemical species to the target tissue.

Abstract: A method and system for a misfire detection acquires (301) a series of acceleration data (302) representative of acceleration behavior of an engine. The data is sampled (304) to obtain acceleration data samples at a rate sufficient to obtain up to fourth-order perturbations of the data. The samples are filtered (322) to provide bandwidth limited samples, which are provided to at least two channels (325, 329). The samples are pattern matched (332) in a first channel to enhance harmonic phenomena and pattern canceled (330) in a second channel to enhance random phenomena. Hard and random misfires are detected (334) dependent on a magnitude of the filtered acceleration data samples. Preferably, a third channel (335) is added to detect multiple misfires.

Abstract: Micro-electro-mechanical system (MEMS) variable capacitor apparatuses, system and related methods are provided.

Abstract: A device for manipulating a molecule in vivo relative to a target tissue includes at least one elongated member having at least two discrete and separately activatable electrodes separated by an insulating material interposed therebetween. The electrodes are configured to establish at least one of a first electromagnetic field between selected electrodes sufficient to manipulate a molecule relative to a target tissue and a second, typically higher-level, electromagnetic field sufficient to cause transient permeability of a cell membrane within the target tissue. A third electromagnetic field may also be applied to cause further translation of the molecule into an electropermeabilized cell and/or manipulated with respect to the tissue. Thus three-dimensional manipulation of the molecule relative to the target tissue may be effected to optimize a desired positioning thereof, such as entry into a cell.

Abstract: The electroporation system and method combine pulses having different characteristics for delivering molecules to cells in vivo. The pulses include a high-intensity pulse for inducing electroporation and a low-intensity pulse to induce electrophoretic molecule movement within an interstitial space, molecule adherence to a cell membrane, and electrophoretic movement of the molecule through the permeabilized membrane. The use of a high-intensity and a low-intensity pulse achieves improved delivery; reduction of intensity and/or duration of pulses for inducing electroporation; and decreased muscle stimulation, tissue damage, and patient discomfort.

Abstract: A system and method for integrating microfluidic components in a microfluidic system enables the microfluidic system to perform a selected microfluidic function. A capping module includes a microfluidic element for performing a microfluidic function. The capping module is stacked on a microfluidic substrate having microfluidic plumbing to incorporate the microfluidic function into the system.

Abstract: Identification and contact information is captured and verified for dissemination. Electronic scals that identify an originator or author of an electronic message or document are inserted in the message or document. The seal forms an identification card for the originator or author based upon the verified contact information. A recipient or viewer of the message or document can view, in the message or document, the embedded seal that comprises a graphic and associated text. A network hyperlink reference from the seal to a server displays a seal verification page. The seal verification page comprises contact information for the originator or author, and other details such as those relating specifically to the message or document. The verified contact information is also used to provide a secure directory of contact information and a facility for printing business cards.

Abstract: MEMS Device having Electrothermal Actuation and Release and Method for Fabricating. According to one embodiment, a microscale switch is provided and can include a substrate and a stationary electrode and stationary contact formed on the substrate. The switch can further include a movable microcomponent suspended above the substrate. The microcomponent can include a structural layer including at least one end fixed with respect to the substrate. The microcomponent can further include a movable electrode spaced from the stationary electrode and a movable contact spaced from the stationary electrode. The microcomponent can include an electrothermal component attached to the structural layer and operable to produce heating for generating force for moving the structural layer.

Abstract: The present invention is a method of electromanipulation for effecting substantially simultaneous electroporation and electromigration of molecules into cells by applying to a cellular target a preselected electrical waveform. The preselected electrical waveform may be formed of at least one curved or linear component either increasing or decreasing in amplitude as a function of time. In a preferred embodiment of the invention the at least one component has a duration no greater than five minutes and a maximum amplitude no greater than 10,000 V/cm. Alternatively, the waveform may also include a substantially constant amplitude component interposed between the increasing and decreasing components. The substantially constant amplitude component may also be applied prior or subsequent to the at least one component.

Abstract: A microfluidic system includes a bubble valve for regulating fluid flow through a microchannel. The bubble valve includes a fluid meniscus interfacing the microchannel interior and an actuator for deflecting the membrane into the microchannel interior to regulate fluid flow. The actuator generates a gas bubble in a liquid in the microchannel when a sufficient pressure is generated on the membrane.

Abstract: A permeable membrane system (10) for the separation of fluid components includes a laminated composition (12) having two sheets (14 and 16) formed from a polymer and positioned adjacent one another to form a fluid passage (18) therebetween. The outside surfaces (20 and 22) of the sheets (14 and 16) are permeable to allow fluid flow from the outside surface (20 and 22) to the fluid passage (18). The outside surface (20 and 22) of the laminated composition (12) includes a plurality of embossed islands spaced from one another to define feed pathways (26) around and between the embossed islands.